Editing Hypothyroidism (section)

==Diagnosis==
{{See also|Thyroid function tests}}
Laboratory testing of thyroid stimulating hormone (TSH) levels in the blood is considered the best initial test for hypothyroidism; a second TSH level is often obtained several weeks later for confirmation.<ref name=So2012>{{cite journal | vauthors = So M, MacIsaac RJ, Grossmann M | title = Hypothyroidism | journal = Australian Family Physician | volume = 41 | issue = 8 | pages = 556–62 | date = August 2012 | pmid = 23145394 | url = https://gplearning.racgp.org.au/content/AFP/12Aug/August_focus_so.pdf }}</ref> Levels may be abnormal in the context of other illnesses, and TSH testing in hospitalized people is discouraged unless thyroid dysfunction is strongly suspected<ref name=Garber/> as the cause of the acute illness.<ref name=NICENG145/> An elevated TSH level indicates that the thyroid gland is not producing enough thyroid hormone, and free T<sub>4</sub> levels are then often obtained.<ref name=Garber/><ref name=NICENG145/><ref name=Brown2013/> Measuring T<sub>3</sub> in the assessment for hypothyroidism is discouraged by the [[American Association of Clinical Endocrinologists]] (AACE) and [[National Institute for Health and Care Excellence]] (NICE).<ref name=Garber/> NICE recommends routine T<sub>4</sub> testing in children where clinically indicated, and in adults only if central hypothyroidism is suspected or the TSH is abnormal.<ref name=NICENG145/> There are several symptom rating scales for hypothyroidism; they provide a degree of objectivity but have limited use for diagnosis.<ref name=Garber/>

{| class="wikitable" style="float: right; border: 1px solid #BBB; margin: .46em 0 0 .2em;"
|-
! TSH !! T<sub>4</sub> !! Interpretation
|-
| Normal || Normal || Normal thyroid function
|-
| Elevated || Low || Overt hypothyroidism
|-
| Normal/low || Low || Central hypothyroidism
|-
| Elevated || Normal || Subclinical hypothyroidism
|}

Many cases of hypothyroidism are associated with mild elevations in [[creatine kinase]] and liver enzymes in the blood. They typically return to normal when hypothyroidism has been fully treated.<ref name=Garber/> Levels of [[cholesterol]], [[low-density lipoprotein]] and [[lipoprotein(a)|lipoprotein (a)]] can be elevated;<ref name=Garber/> the impact of subclinical hypothyroidism on lipid parameters is less well-defined.<ref name=Pearce/>

Very severe hypothyroidism and myxedema coma are characteristically associated with [[hyponatremia|low sodium levels in the blood]] together with elevations in [[Vasopressin|antidiuretic hormone]], as well as [[Acute kidney injury|acute worsening of kidney function]] due to several causes.<ref name=Klubo/> For most causes, however, it is unclear if the relationship is causal.<ref>{{cite journal | vauthors = Pantalone KM, Hatipoglu BA | title = Hyponatremia and the Thyroid: Causality or Association? | journal = Journal of Clinical Medicine | volume = 4 | issue = 1 | pages = 32–6 | date = December 2014 | pmid = 26237016 | pmc = 4470237 | doi = 10.3390/jcm4010032 | doi-access = free }}</ref>

A diagnosis of hypothyroidism without any [[Thyroid nodule|lumps or masses]] [[Palpation|felt]] within the thyroid gland does not require thyroid imaging; however, if the thyroid feels abnormal, diagnostic imaging is then recommended.<ref name=So2012/> The presence of antibodies against [[thyroid peroxidase]] (TPO) makes it more likely that thyroid nodules are caused by autoimmune thyroiditis, but if there is any doubt, a [[fine-needle aspiration|needle biopsy]] may be required.<ref name=Garber/>

===Central===
If the TSH level is normal or low and serum free T<sub>4</sub> levels are low, this is suggestive of '''central hypothyroidism''' (not enough TSH or TRH secretion by the pituitary gland or hypothalamus, respectively). There may be other features of [[hypopituitarism]], such as [[menstrual cycle]] abnormalities and [[adrenal insufficiency]]. There might also be symptoms of a [[pituitary adenoma|pituitary mass]] such as [[headache]]s and vision changes. Central hypothyroidism should be investigated further to determine the underlying cause.<ref name=Persani2012/><ref name=So2012/>

===Overt===
In overt primary hypothyroidism, TSH levels are high and T<sub>4</sub> levels are low. Overt hypothyroidism may also be diagnosed in those who have a TSH on multiple occasions of greater than 5mIU/L, appropriate symptoms, and only a borderline low T<sub>4</sub>.<ref name=Don2009>{{cite book|last1=Dons|first1=Robert F.|last2=Wians|first2=Frank H. Jr.|title=Endocrine and metabolic disorders clinical lab testing manual|date=2009|publisher=CRC Press|location=Boca Raton|isbn=9781420079364|page=10|edition=4th|url=https://books.google.com/books?id=rS41IwpI-hIC&pg=PA10}}</ref> It may also be diagnosed in those with a TSH of greater than 10mIU/L.<ref name=Don2009/>

===Subclinical===
Subclinical hypothyroidism is a biochemical diagnosis characterized by an elevated serum TSH level, but with a normal serum free thyroxine level.<ref name="Peters 2017">{{cite journal |last1=Peeters |first1=Robin P. |title=Subclinical Hypothyroidism |journal=New England Journal of Medicine |date=29 June 2017 |volume=376 |issue=26 |pages=2556–2565 |doi=10.1056/NEJMcp1611144|pmid=28657873 |s2cid=56184355 }}</ref><ref name=Bona2013>{{cite journal | vauthors = Bona G, Prodam F, Monzani A | title = Subclinical hypothyroidism in children: natural history and when to treat | journal = Journal of Clinical Research in Pediatric Endocrinology | volume = 5 Suppl 1 | issue = 4 | pages = 23–8 | year = 2013 | pmid = 23154159 | pmc = 3608012 | doi = 10.4274/jcrpe.851 | type = Review }}</ref><ref name=Fatourechi/> The incidence of subclinical hypothyroidism is estimated to be 3-15% and a higher incidence is seen in elderly people, females and those with lower iodine levels.<ref name="Peters 2017" /> Subclinical hypothyroidism is most commonly caused by autoimmune thyroid diseases, especially [[Hashimoto's thyroiditis]].<ref name=Baumgartner2014>{{cite journal | vauthors = Baumgartner C, Blum MR, Rodondi N | title = Subclinical hypothyroidism: summary of evidence in 2014 | journal = [[Swiss Medical Weekly]] | volume = 144 | pages = w14058 | date = December 2014 | pmid = 25536449 | doi = 10.4414/smw.2014.14058 | type = Review | doi-access = free }}</ref>  The presentation of subclinical hypothyroidism is variable and classic signs and symptoms of hypothyroidism may not be observed.<ref name=Bona2013/> Of people with subclinical hypothyroidism, a proportion will develop overt hypothyroidism each year. In those with detectable antibodies against thyroid peroxidase (TPO), this occurs in 4.3%, while in those with no detectable antibodies, this occurs in 2.6%.<ref name=Garber/> In addition to detectable anti-TPO antibodies, other risk factors for conversion from subclinical hypothyroidism to overt hypothyroidism include female sex or in those with higher TSH levels or lower level of normal free T<sub>4</sub> levels.<ref name="Peters 2017" /> Those with subclinical hypothyroidism and detectable anti-TPO antibodies who do not require treatment should have repeat thyroid function tested more frequently (e.g. every 6 months) compared with those who do not have antibodies.<ref name=So2012/><ref name="Peters 2017" />

===Pregnancy===
During pregnancy, the thyroid gland must produce 50% more thyroid hormone to provide enough thyroid hormone for the developing fetus and the expectant mother.<ref name="Negro2014">{{cite journal | vauthors = Negro R, Stagnaro-Green A | title = Diagnosis and management of subclinical hypothyroidism in pregnancy | journal = BMJ | volume = 349 | issue = 10 | pages = g4929 | date = October 2014 | pmid = 25288580 | doi = 10.1136/bmj.g4929 | s2cid = 21104809 }}</ref>  In pregnancy, free thyroxine levels may be lower than anticipated due to increased binding to [[thyroid binding globulin]] and decreased binding to [[albumin]]. They should either be corrected for the stage of pregnancy,<ref name=Stagnaro/> or total thyroxine levels should be used instead for diagnosis.<ref name=Garber/> TSH values may also be lower than normal (particularly in the [[first trimester]]) and the normal range should be adjusted for the stage of pregnancy.<ref name=Garber/><ref name=Stagnaro/>

In pregnancy, subclinical hypothyroidism is defined as a TSH between 2.5 and 10&nbsp;mIU/L with a normal thyroxine level, while those with TSH above 10&nbsp;mIU/L are considered to be overtly hypothyroid even if the thyroxine level is normal.<ref name=Stagnaro/> Antibodies against TPO may be important in making treatment decisions, and should, therefore, be determined in women with abnormal thyroid function tests.<ref name=Garber/> Determination of TPO antibodies may be considered as part of the assessment of [[recurrent miscarriage]], as subtle thyroid dysfunction can be associated with pregnancy loss,<ref name="Garber" /> but this recommendation is not universal,<ref>{{cite journal | title = Evaluation and treatment of recurrent pregnancy loss: a committee opinion | journal = Fertility and Sterility | volume = 98 | issue = 5 | pages = 1103–11 | date = November 2012 | pmid = 22835448 | doi = 10.1016/j.fertnstert.2012.06.048 | author1 = Practice Committee of the American Society for Reproductive Medicine | s2cid = 30527688 | doi-access = free }}</ref> and the presence of thyroid antibodies may not predict future outcomes.<ref name="RCOG">{{cite web |title=Recurrent Miscarriage, Investigation and Treatment of Couples |url=https://www.rcog.org.uk/en/guidelines-research-services/guidelines/gtg17/ |website=Royal College of Obstetricians & Gynaecologists }}</ref>